|
rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0039194,
umls-concept:C0085358,
umls-concept:C0085536,
umls-concept:C0111208,
umls-concept:C0282536,
umls-concept:C0332197,
umls-concept:C0441994,
umls-concept:C0449864,
umls-concept:C1332717,
umls-concept:C1413244,
umls-concept:C1706438,
umls-concept:C1707520,
umls-concept:C1879547,
umls-concept:C2698600
|
|
pubmed:issue |
6
|
|
pubmed:dateCreated |
2001-3-12
|
|
pubmed:abstractText |
To examine the role of CTLA-4 in controlling Ag-specific CD8(+) T cell activation, TCR-transgenic/CTLA-4 wild-type or -deficient mice were generated in a recombination-activating gene 2-deficient background. Naive T cells from these mice responded comparably whether or not CTLA-4 was expressed. In contrast, primed T cells responded more vigorously if they lacked CTLA-4 expression. We took advantage of the difference between naive and primed T cell responses to approach the mechanism of CTLA-4 function. Single-cell analyses demonstrated that a greater fraction of CTLA-4-deficient cells responded to a fixed dose of Ag compared with CTLA-4-expressing cells, whereas the magnitude of response per cell was comparable. A shift in the dose-response curve to APCs was also observed such that fewer APCs were required to activate CTLA-4-deficient T cells to produce intracellular IFN-gamma and to proliferate. These results suggest that CTLA-4 controls the threshold of productive TCR signaling. Biochemical analysis comparing stimulated naive and primed TCR-transgenic cells revealed no obvious differences in expression of total CTLA-4, tyrosine-phosphorylated CTLA-4, and associated Src homology domain 2-containing protein tyrosine phosphatase. Thus, the biochemical mechanism explaining the differential inhibitory effect of CTLA-4 on naive and primed CD8(+) T cells remains unclear.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
AIM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adjuvants, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation,
http://linkedlifedata.com/resource/pubmed/chemical/CTLA-4 Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Ctla4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoconjugates,
http://linkedlifedata.com/resource/pubmed/chemical/Immunosuppressive Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Rag2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell,
http://linkedlifedata.com/resource/pubmed/chemical/V(D)J recombination activating...,
http://linkedlifedata.com/resource/pubmed/chemical/abatacept
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Mar
|
|
pubmed:issn |
0022-1767
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
15
|
|
pubmed:volume |
166
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
3900-7
|
|
pubmed:dateRevised |
2011-11-17
|
|
pubmed:meshHeading |
pubmed-meshheading:11238634-Adjuvants, Immunologic,
pubmed-meshheading:11238634-Animals,
pubmed-meshheading:11238634-Antigens, CD,
pubmed-meshheading:11238634-Antigens, Differentiation,
pubmed-meshheading:11238634-CD8-Positive T-Lymphocytes,
pubmed-meshheading:11238634-CTLA-4 Antigen,
pubmed-meshheading:11238634-DNA-Binding Proteins,
pubmed-meshheading:11238634-Immunization,
pubmed-meshheading:11238634-Immunoconjugates,
pubmed-meshheading:11238634-Immunosuppressive Agents,
pubmed-meshheading:11238634-Interphase,
pubmed-meshheading:11238634-Lymphocyte Activation,
pubmed-meshheading:11238634-Mice,
pubmed-meshheading:11238634-Mice, Inbred C57BL,
pubmed-meshheading:11238634-Mice, Inbred DBA,
pubmed-meshheading:11238634-Mice, Knockout,
pubmed-meshheading:11238634-Mice, Transgenic,
pubmed-meshheading:11238634-Protein Tyrosine Phosphatases,
pubmed-meshheading:11238634-Receptors, Antigen, T-Cell,
pubmed-meshheading:11238634-Transfection,
pubmed-meshheading:11238634-Tumor Cells, Cultured,
pubmed-meshheading:11238634-src Homology Domains
|
|
pubmed:year |
2001
|
|
pubmed:articleTitle |
Absence of CTLA-4 lowers the activation threshold of primed CD8+ TCR-transgenic T cells: lack of correlation with Src homology domain 2-containing protein tyrosine phosphatase.
|
|
pubmed:affiliation |
Department of Pathology, University of Chicago, Chicago, IL 60637, USA. tgajewsk@medicine.bsd.uchicago.edu
|
|
pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|
